This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The efficacy of a DNA prime/rAd5 boost vaccination protocol against repeated low-dose challenge with R5 SHIVSF162P3 was evaluated. Multiple low-dose exposures mimic more closely the dynamics of natural HIV-1 transmission, and R5 viruses represent the vast majority of sexually transmitted cases. Sixteen animals were divided into two groups. Group A consisted 8 animals primed with DNA 2 times and boosted once with rAd5 on 0, 4 weeks and 8 weeks respectively. In Group B, 8 animals were also injected IM with a sterile saline like the experimental group on 0, 4 and 8 weeks. We are mid-way through of weekly IVAG challenges for 20 weeks with 300 TCID50 SHIVSF162P3N. Preliminary results are 3/8 of the vaccine group and 5/8 controls are infected.